Studies on the mechanism of TSH desensitization in thyroid tissue. Studies are ongoing using cultured human and dog thyroid cells to examine the mechanism whereby desensitization of the cAMP response to TSH is produced. In previous studies we determined that inhibitors of ADP-ribosylation reactions including nicotinamide, thymidine and bromodyoxiuridine prevented the development of TSH desensitization. It has further been found that TSH stimulates ADP-ribosylation of endogenous ADP-ribosylated material in the thyroid cells. The relationship between the requirement for a new protein synthesis, previously found necessary for TSH desensitization, and the ADP-ribosylation mechanism is also being investigated. Thyroid stimulating immunoglobulin bioassay using cultured human thyroid cells. Studies are continuing to determine the clinical usefulness of this assay. In addition, it is planned to use this assay to compare the mechanisms of action of TSK and TSI, particularly at the level of the plasma membrane.